Irtisha Singh, PhD

Education and Training

• Vellore Institute of Technology, B.Tech, Bioinformatics, 2008
• Carnegie Mellon University, MS, Computational Biology, 2009
• Cornell University, Weill Cornell Medical College and Memorial Sloan Kettering Cancer Center, PhD, Computational Biology and Medicine, 2017
• Baylor College of Medicine, Postdoc, Molecular and Human Genetics, 2019

Research Interests

• The primary goal of Dr. Singh’s laboratory is to model and understand the molecular basis of tumor development, progression, and response to therapy. Her laboratory applies and develop computational, molecular, and chemical biology approaches to understand mechanisms of transcriptional deregulation in cancer and the consequences of targeting the chromatin and transcription apparatus on cancer cell state. A parallel focus of her laboratory is to develop and use cellular engineered models of cancer cell state to discern the role of tumor microenvironment supporting neoplastic transformation. The immediate focus of Singh laboratory is:
• 1. Cancer epigenetics: Understand chromatin-directed oncogenic transformation in glioblastoma. Specifically, we aim to systematically characterize the oncogenic role of candidate transcription factors (TFs) as drivers of tumorigenesis in glioblastoma and identify their downstream target oncogenes with a potential therapeutic window.
• 2. Bioengineered tumor organoids: Develop and validate bioengineered glioblastoma 3D organoids from glioblastoma stem cells (GSCs). We aim to utilize these bioengineered glioblastoma 3D organoids to understand the molecular regulation of GSCs in a microenvironment mimicking its native surroundings.
• 3. Cancer RNA biology: Compile a comprehensive atlas of intronic polyadenylation (IPA) isoforms across 38 cancer types present in The Cancer Genome Atlas (TCGA), followed by determination of IPA sites that are regulated differently in tumors compared to their normal. Furthermore, we will assess the functional consequences of IPA dysregulation in different cancer types.
• 4. Regenerative medicine: Utilize genome wide sequencing assays (transcriptomics and chromatin accessibility) to understand complex cell-biomaterials interactions. Specifically, we will utilize these omics-based approaches to provide an unbiased global view of the cellular activity with pivotal insights about the affected cellular pathways to optimize synthetic biomaterials for tissue engineering.

Representative Publications

• Gaharwar AK, Singh I, Khademhosseini A, Engineered Biomaterials for In situ Tissue Regeneration. Nature Review Materials (In press) https://doi.org/10.1038/ s41578-020-0209- x
• Carrow J., Singh KA, Jaiswal MK, Ramirez A, Lokhande A, Yeh A, Sarkar TA, Singh I*, Gaharwar AK*. Photothermal Modulation of Human Stem Cells Using Light-responsive 2D Nanomaterials. Proceedings of the National Academy of Sciences, 117 (24), 13329-13338 (2020)
• *Co-corresponding authors
• ChimeneD, Miller L, Cross L, Jaiswal MK, Singh I, Gaharwar AK. Nanoengineered Osteoinductive Bioink for 3D Bioprinting Bone Tissue. ACS Applied Materials & Interfaces, 12 (14), 15976-15988 (2020)
• Sin-Chan P*, Mumal I*, Suwal T, Ho B, Xiaolian F, Singh I, Lu M, Torchia J, Lovejoy DB, Guilhamon P, Fouladi M, Lassaletta A, Afzal S, Philips J, Solano-Paez P, Lindsey M. Hoffman, Van Meter T, Leary S, Nakamura H,  Massimi L, Grundry R, Fangusaro J, Johnston D, Hwang E, Wang Y, Scharnhorst D, Camelo-Piragua S, Reddy A, Gillespie Y, Catchpoole D, Hansford J, Gil da Costa MJ, Michaud J, Levy JM, Ellezam B, Ramanujachar R, Lindsay HB, Singh SK, Jabado N, Kleinman CL, Taylor MD, Hawkins CE, Bouffet E, Arrowsmith CH, Dirks PB, Li XN, Lin CY, Rich JN, Mack SC, Huang A., “A C19MC-MYCN-LIN28A oncogenic circuit driven by hijacked super-enhancers represents a distinct therapeutic vulnerability in ETMRs”, Cancer Cell 36 (1), 51-67. e7 (2019)
• Mack SC*,Singh I*, Wang X*, Hirsch R, Wu Q, Bernatchez JA, Zhu Z, Gimple RC, Kim LJY, Morton A, Lai S, Qiu Z, Villagomez R, Prager BC, Bertrand KC, Mah C, Zhou W, Lee C, Barnett GH, Vogelbaum MA, Sloan AE, Chavez L, Bao S, Scacheri PC, Siqueira-Neto JL, Lin CY#, Rich JN#,“Chromatin landscapes reveal developmentally encoded transcriptional states that define glioblastoma”, Journal of Experimental Medicine, 216 (5), 1071 (2019)
• *Co-first authors
• Fulciniti M*, Lin CY*, Samur MK, Lopez MA, Singh I, Lawlor MA, Szalat RE,  Ott CJ, Avet-Loiseau H, Anderson KC,  Young RA, Bradner JE, Munshi NC, “Non-overlapping control of transcriptome by Promoter and Super-Enhancer-Associated Dependencies”, Cell Reports 25: 3693-3705.e6 (2018)
• Lee S*, Singh I*, Lee S, Tisdale S, Abdel-Wahab O, Leslie C, Mayr C, “Widespread intronic polyadenylation inactivates tumor suppressor genes in leukemia”, Nature 561, 127–131 (2018)
• *Co-first authors
• Singh I, Lee S, Sperling A, Samur MK, Tai Y, Fulciniti M, Munshi N, Mayr C, Leslie C “Widespread intronic polyadenylation diversifies immune cell transcriptomes”, Nature Communications 9: 1716 (2018)
• Carrow J, Cross L, Reese R, Jaiswal M, Gregory C, Kaunas R, Singh I*, Gaharwar A*, “Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates”, Proceedings of the National Academy of Sciences 115,E3905-E3913(2018)
• *Co-corresponding authors
• Pelossof R, Singh I, Yang J, Weirauch M, Hughes T, Leslie C “Learning the recognition code for transcription factor and RNA-binding protein families from high-throughput binding assays”, Nature Biotechnology 33, 1242–1249(2015)
• Han Y, Vidigal J, Mu P, Yao E, Singh I, Gonzalez A, Concepcion C, Bonetti C, Ogrodowski P, Carver B, Selleri L, Betel D, Leslie C, Ventura A “An allelic series of miR-17~92 mutant mice uncovers functional specialization and cooperation among members of a miRNA polycistron”, Nature Genetics 47, 766–775(2015)
• Curanovic D, Cohen M, Singh I, Slagle CE, Leslie CS, Jaffrey SR “Global profiling of stimulus-induced polyadenylation in cells using a poly (A) trap” in Nature Chemical Biology 9, 671–673(2013)